Our Correspondent
Evidence is growing that some coronavirus variants could evade immune responses triggered by vaccines and previous infections. Researchers are trying to make sense of a tsunami of lab studies released this week that raise concerns about some emerging variants and mutations, according to a report in Nature.
“Some of the data I’ve seen in the last 48 hours have really scared me,” says Daniel Altmann, an immunologist at Imperial College London, who worries that some of results could portend a reduction in the effectiveness of COVID-19 vaccines.
But the picture is murky, Altmann and other scientists emphasize. The studies — which examined the blood of small numbers of people who had recovered from COVID-19 or received a vaccine — probed only their antibodies’ capacity to ‘neutralise’ variants in laboratory tests, and not the wider effects of other components of their immune response.
Neither do the studies indicate whether the changes in antibody activity make any difference to the real-world effectiveness of vaccines or the likelihood of reinfection. “Are these changes going to be important? I really don’t know,” says Paul Bieniasz, a virologist at the Rockefeller University in New York City, who co-led one of the studies, the report on January 21 said.
Much of the concern centres around a variant that researchers identified in South Africa in late 2020. A team led by Tulio de Oliveira, a bioinformatician at the University of KwaZulu-Natal in Durban, South Africa, linked the variant — called 501Y.V2 — to a fast-growing epidemic in Eastern Cape province that has since spread across South Africa and into other countries. The lineage carries many mutations in the SARS-CoV-2 spike protein — the immune system’s prime target, which allows the virus to identify and infect host cells — including some changes linked to weakened antibody activity against the virus2,3.
The Eastern Cape was hit hard by South Africa’s first COVID-19 wave, and researchers wondered whether the rapid spread of 501Y.V2 could be partly explained by its ability to elude previously established immune responses.
To investigate this, de Oliveira, virologist Alex Sigal at the Africa Health Research Institute in Durban and other colleagues isolated 501Y.V2 viruses from people infected with the variant4. They then tested the variant samples against serum — the antibody-containing portion of blood — taken from six people who had recovered from COVID-19 caused by other versions of the virus. This convalescent serum tends to contain neutralizing, or virus-blocking, antibodies that can prevent infection. The researchers found that the convalescent serum was much worse at neutralizing 501Y.V2 than at neutralising variants that circulated earlier in the pandemic. Some people’s plasma performed better against 501Y.V2 than did others’, but in all cases, the neutralizing power was substantially weakened, says de Oliveira. “It’s extremely worrying.”
In a separate study, a team led by virologist Penny Moore at the National Institute for Communicable Diseases and the University of the Witwatersrand in Johannesburg, South Africa, probed the effects of convalescent serum on various combinations of spike mutations found in 501Y.V2. They did this using a ‘pseudovirus’ — a modified form of HIV that infects cells using the SARS-CoV-2 spike protein.
These experiments showed that 501Y.V2 contains mutations that blunt the effects of neutralising antibodies that recognise two key regions of spike: its receptor-binding and N-terminal domains. Pseudoviruses with the full package of 501Y.V2 mutations were fully resistant to convalescent serum from 21 out of 44 participants, and were partly resistant to the vast majority of people’s sera, Moore’s team found.
There is now proof of several reinfections with 501Y.V2 in South Africa, says de Oliveira. It seems increasingly likely that the variant’s ability to spread in places hit hard by earlier waves of COVID-19 is being driven, in part, by its capacity to evade immune responses that developed in response to earlier versions of the virus.
